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Human T-cell leukemia virus type1 (HTLV-1)
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Tax
p30
HBZ |
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-
Tax expressing cells have reduced levels of Ku80 mRNA [45];
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Tax constitutively activates DNA-PK and attenuates ATM signaling in response to DNA damage [46,47];
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Tax binds and sequesters other factors in damage-independent nuclear foci, including BRCA1, and MDC1 [48];
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Tax induces DNA DSBs during DNA replication, thus promoting genetic instability while also activating the NF-κB pathway to eventually inhibit the HR DNA repair pathway [49];
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Tax alters the levels of key cellular factors such as DNA polymerase β and PCNA [50,51,52,53];
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Tax inactivates transcription of telomerase, and this in turn can leave unprotected DNA ends that are more susceptible to recombination and translocation events, in turn leading to karyotypic abnormalities [54];
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p30 inhibits the conservative HR DNA repair by targeting the MRE11/RAD50/NBS1 complex, and that in turn promotes the error-prone NHEJ DNA-repair pathway [55];
-
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HBZ interacts with Ku70 and Ku80 and reduces repairs of DNA DSBs via NHEJ [56].
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Human papillomavirus (HPV)
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E1
E2
E7 |
-
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E7 through its LXCXE motif directly binds to ATM, thus promoting both activation of CHK2 and a low level of caspase activation [57];
-
-
HPV16 E2 interacts and co-localizes at centrosomes in mitosis with TOPBP1, affecting ATR damage signaling directly [58,59];
-
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E1 and E2 co-localize with ATM, ATRIP, MRN, Ku70/86, CHK2 and CHK1 at integrated HPV18 genome replication centers, leading to the activation of DDR pathway [60];
-
-
E6 and E7 can induce DNA damage and promote γH2AX focus formation [61];
-
-
HPV16 E7 appears to accelerate proteo-lytic turnover of the ATR activator claspin, thus promoting mitotic entry in the presence of DNA damage and it also activates DDR pathways [62,63];
-
-
E7 from “high-risk” HPV types might activate the FA pathway and indeed cervical carcinoma tissue exhibits enhanced nuclear FANCD2 focus formation, and this effect is enhanced by the E6 protein [64];
-
-
HPV16 E7 expression in FA-deficient cells increases chromosomal instability and apoptosis [62,65].
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Hepatitis B Virus (HBV)
|
HBX |
-
-
HBX directly binds DDB1 [66] and this leads to severely reduced NER [67,68,69,70];
-
-
HBX reduces NER activity by directly interacting with some proteins of the TFIIH nucleotide basal excision repair complex [71,72,73,74,75], and this may downregulate the expression levels of both XPB and XPD [72];
-
-
HBX directly binds to p53 and inhibits its anticancer functions [76,77,78,79], while also blocking its association with transcription factors belonging to the DDRs, like ERCC3/XPD and ERCC2/XPB [73,78];
-
-
HBV infection reduces the protein level of Mre11 thus causing genome instability [80];
-
-
HBV viral DNA contains sequences motifs that bind to PARP-1 hampering its DNA repair activity, and this may increase the replication efficiency of HBV and promote the development of HCC [81].
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Hepatitis C virus (HCV)
|
Core protein
NSP5A
UHCV57.3 |
-
-
HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11-NBS1-Rad50 complex, thus hampering ATM activation and inhibiting proper DNA binding of critical enzymes involved in repair pathways [82];
-
-
NSP5A binds to RAD51AP1 and this eventually results in reduced activity of the RAD51/RAD51AP1/UAF1 complex and consequently increased sensitivity to DNA damage of HCV-infected cells [83];
-
-
Inducible expression of UHCV57.3 results in inhibition of histone H4 methylation/acetylation and H2AX phosphorylation and inhibition of DNA damage repair functions [84].
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Epstein–Barr virus (EBV)
|
EBNA-1
LMP-1
BZLF1
BGLF5
EBNA-3C
EBNA-LP |
-
-
EBNA-1 promotes the generation of ROS that cause DNA damage [85,86];
-
-
LMP-1 downregulates ATM, eventually resulting in CHK2 phosphorylation and abrogation of G2 checkpoint. LMP-1 blocks also DNA repair by activating the PI3K/Akt pathway that results in reduced activity of FOXO3a [87];
-
-
EBV inactivates p53, leading to ATM-mediated checkpoints evasion, holding the host cell in S phase and thus facilitating virus replication [88];
-
-
The IE lytic transactivator BZLF1 recruits Cul2- and/or Cul5- CRLs, to induce p53 degradation [89];
-
-
Early lytic viral protein BGLF5 directly damages the cellular DNA and consequently hampers the expression of several DNA-repair genes [90];
-
-
BGLF5 contributes to the production of linear viral genomes and it promotes genomic instability during lytic replication. [91,92];
-
-
EBNA-3C inhibits DDR in normally proliferating lymphoblastoid cell lines [93];
-
-
EBV infection reduces apoptosis induced following DNA damage in Burkitt’s lymphoma-derived B-cells through expression of EBNA-3A and EBNA-3C, which in turn reduce BIM and NOXA expression [94];
-
-
EBNA-LP interacts with DNA-PK and co-immunoprecipitates with HA95 [95].
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Kaposi’s sarcoma-associated herpesvirus (KSHV) or Human herpesvirus 8 (HHV-8)
|
V-cyclin |
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